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研究生:徐佳嫺
研究生(外文):Jia-Shian Shiu
論文名稱:一、早期塑化劑暴露與孩童智力表現之相關探討;二、產前全氟碳化物暴露與孩童注意力缺陷過動症症狀之相關探討
論文名稱(外文):Part I. The association between early exposure to phthalates and intellectual performance in young childrenPart II. Prenatal exposure to perfluorinated chemicals and attention deficit/hyperactivity symptoms in children at 7 years of age
指導教授:陳保中陳保中引用關係
指導教授(外文):Pau-Chung Chen
口試委員:郭育良高淑芬謝佳容謝武勳
口試委員(外文):Yue-Liang GuoShur-Fen GauChia-Jung HsiehWu-Shiun Hsieh
口試日期:2013-06-28
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:職業醫學與工業衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:50
中文關鍵詞:智力表現塑化劑鄰苯二甲酸單丁酯兒童注意力缺陷過動症全氟化合物兒童
外文關鍵詞:intelligencemono-n-butyl phthalate (MBP)phthalatesyoung childrenattention deficit/hyperactivity disorder (ADHD)perfluorinated compounds (PFCs)young children
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第一部份
背景:在動物實驗研究中發現鄰苯二甲酸鹽暴露可能導致動物神經行為缺陷。
而近期研究也指出環境中的汙染物與兒童的智商有關,然而環境中塑化劑暴露對於兒童智力的表現研究更需深入探討。

目的:本研究為探討早期塑化劑暴露對於兒童智力之影響。

材料與方法:本研究團隊從Taiwan Birth Panel Study (TBPS) 中170位兒童作為研究對象。收集其尿液樣本,以極致液相層析串聯式質譜儀(ultra-high performance liquid chromatography tandem mass spectrometry, UPLC-MS/MS)測量四種塑化劑代謝物之濃度,其代謝物分別有mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP) 及 mono-2-ethylhexyl phthalate (MEHP)。另外,以魏氏兒童智力量表第四版 (Wechsler intelligence scale for children fourth edition, WISC-IV) 量測智力分數,其指標包含全量表智商 (full scale IQ, FSIQ)、語文理解指數 (verbal comprehension index, VCI)、知覺推理指數 (perceptual reasoning index, PRI)、工作記憶指數 (working memory index, WMI) 及處理速度指數 (processing speed index, PSI)。統計方法上,使用多變相線性回歸,並校正性別、週數、臍帶血中鉛(lead)與古丁尼(cotinine)濃度、母親年齡、母親智商、母親教育程度、0-3歲兒童家庭物理環境評估量表(Infant/Toddler HOME of Home Observation for Measurement of the Environment Inventory, IT-HOME)分數,以及家庭年收入等干擾因子。而在多變相邏輯式回歸分析中,我們將所有智力指數低於第1四分位數作為較低組,大於等於第1四分位數作為較高組,分析塑化劑與兒童的智力指數之相關。

結果:在多變相線性回歸分析中,本研究發現尿液中MBP和FSIQ、PRI及PSI有統計顯著負相關。另外,隨著每log10 MBP(μg/g-creatinine)的濃度增加,導致全量表FSIQ智商分數較低的勝算比(odds ratio, OR)為4.36,其百分之九十五信賴區間(95% confidence interval, 95% CI)為1.22 - 15.59。導致知覺推理指PRI數較低的勝算比為3.69 (OR = 3.69; 95% CI = 1.1012.39)。導致工作記憶WMI指數較低的勝算比為3.69 (OR = 3.69; 95% CI = 1.10 - 12.40)。導致處理速度PSI指數較低的勝算比為4.88 (OR = 4.88; 95% CI = 1.47 - 16.25)。

結論:本研究發現早期暴露塑化劑對於兒童智力表現可能有負面影響,因此對於環境中塑化劑之暴露來源應更加謹慎;而未來尚需要更多研究來驗證其因果關係。

第二部份
背景:全氟化合物(perfluorinated chemicals; PFCs)是一種環境中持久污染物,可以穿過胎盤屏障進入胎兒循環。動物研究指出,成年小鼠暴露全氟碳化物可能導致神經行為缺陷。然而目前探討全氟辛酸(perfluorooctanoic acid, PFOA)、全氟辛烷磺酸(perfluorooctyl sulfonate, PFOS)暴露與兒童注意力缺陷過動症症狀(attention deficit hyperactivity disorder; ADHD)的流行病學研究結果有限且無明確定論。

目的:本研究主要目的為探討臍帶血中全氟辛烷磺酸(PFOA)、全氟辛烷磺酸(PFOS)、全氟壬酸(perfluorononanoic acid; PFNA)和全氟酸(perfluoroundecanoic acid; PFUA)與兒童注意力缺陷過動症症狀之相關性。

方法:本研究對象為Taiwan Birth Panel Study (TBPS)及 Taiwan birth cohort study (TBCS)共計282對母親與孩童。研究對象來自位於台北、雲林、嘉義、台南、高雄、台東的醫療中心、地區醫院以及診療所的生產婦女,於產後進行結構式問卷訪談,並於生產時收集胎兒臍帶血樣本。臍帶血血漿中全氟碳化合物之濃度以極致效能液相層析/串聯式譜儀(ultra-high performance liquid chromatography tandem mass spectrometry, UPLC-MS/MS)測量。以注意力缺陷過動症中文版Swanson, Nolan, and Pelham, Version IV (SNAP-IV)量表、長處與困難問卷(Strengths and Difficulties Questionnaire; SDQ)以及兒童行為檢核表(Child Behavior Checklist; CBCL)評估注意力缺陷過動症之特徵情形。統計方法上,使用多變項回歸分析,校正性別、哺餵母乳、母親年齡、母親教育程度後、母親懷孕期間二手煙及飲酒暴露、胎次、家庭年收入、週數、出生體重、臍帶血中鉛濃度等潛在干擾因子,探討全氟碳化合物濃度與兒童注意力缺陷過動症之相關。並使用分層分析,以50、75、90百分位作為切點,將PFCs濃度分為由低到高四個程度,探討其劑量效應。

結果:PFOA,PFOS,PFNA和PFUA濃度的中位數與四分位距(IQR)分別為0.75(1.9),3.7(3.5),1.29(4.3),2.86(11.0)ng/mL。本研究發現,全氟壬酸PFNA和SNAP-IV量表中的注意力不集中(inattention)以及對立違抗性障礙(oppositional defiant disorder)呈顯著負相關。

結論: PFNA與注意力不集中及對立違抗性障礙之間發現負相關結果。未來需要更多的研究來闡明因果關係。

Part I.

Abstract

Background: Phthalate exposure is associated with neurobehavioral deficits in animals. Recent evidences indicated that early exposure to environmental pollutants may be detrimental to intelligence quotient (IQ) in children. However, examine the impact of phthalate exposure on children’s intelligence needs more explore.

Objectives: The purpose of this study is to evaluate the intellectual effect of early phthalate exposure in young children.

Methods: A total of 170 children from the Taiwan Birth Panel Study (TBPS) were followed up in northern Taiwan. We collected urine samples and measured phthalate metabolites including mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and mono-2-ethylhexyl phthalate (MEHP) by ultra-high performance liquid chromatography tandem mass spectrometry. We used the Wechsler intelligence scale 4th edition (WISC-IV), whose indicates including full scale IQ (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI) and processing speed index (PSI), to assess these children’s intelligence. To examine the association between phthalate concentrations and children’s intelligence, we used multiple linear regression models to control confounders including children gender, gestational age, cotinine and lead level in cord blood, maternal age, maternal intelligence, maternal education level, Infant/Toddler HOME of Home Observation for Measurement of the Environment Inventory, (IT-HOME) score and yearly income. In logistic regression models, we categorized the all IQ indicates which score less than lower quartile (Q1) as lower WISC-IV score.

Results: We found negative significant associations between MBP concentration and full scale IQ (FSIQ), perceptual reasoning index (PRI), and processing speed index (PSI) in multiple linear regression models. There were significantly higher risks of have lower quartile FSIQ (OR = 4.36, 95% CI=1.22 - 15.59), PRI (OR = 3.69; 95% CI = 1.10 - 12.39), WMI (OR = 3.69; 95% CI = 1.10 - 12.40), and PSI (OR = 4.88; 95% CI = 1.47 - 16.25) per log10 MBP concentration (μg/g-creatinine), respectively.

Conclusions: Early childhood exposure to phthalates may have an adverse effect on children’s intellectual performance. Further study is needed to elucidate the mechanism between phthalates and children’s intelligence.

Part II.

Abstract

Background: Perfluorinated compounds (PFCs), persistent pollution in environment, can cross the placental barrier and enter fetal circulation. Animal studies report exposure to the PFCs can give irreversible change in mouse brain and affect fetal growth and development. The association between perfluorooctanoic acid (PFOA) and perfluorooctyl sulfonate (PFOS) exposure and ADHD symptoms is controversial in epidemiological studies.

Objectives: We evaluated the association between prenatal exposures to PFOA, PFOS, perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) and ADHD symptoms.

Methods: A total of 282 mother–newborn pairs from various medical facilities, which included three medical centers, one local hospital, and eight clinics, recruited from May 2004 to July 2005, and completed the all follow-up interviews. Cord blood samples were collected at birth and analyzed for PFOA, PFOS, perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) by ultra-high performance liquid chromatography/tandem mass spectrometry. When the children were 7 years of age, we assessed children behavioral health by using the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), the Strengths and Difficulties Questionnaire (SDQ), and the Child Behavior Checklist (CBCL). We divided PFCs in four categories, with cut points at the 50th (the reference category), 75th, and 90th percentiles in linear regression model to examine the relationship between nature log transformed PFCs concentrations and rating scales.

Results: After adjusting for potential confounding factors, we found that increased PFNA concentrations were inversely associated with inattention and oppositional defiant disorder in SNAP.

Conclusions: PFNA are protected with inattention and oppositional defiant disorder in SNAP, but not found in CBCL and SDQ. More studies are needed to elucidate the causal relationship.

Part I.

Contents

摘要........ii
Abstract........iv
Contents........vi
Contents of figures........vii
Contents of tables........viii
Introduction........1
Materials and Methods........2
Study Population and Design........2
Phthalate metabolite in urine........2
Measurement of Intelligence........3
Statistical Analysis........4
Results........5
Discussion........7
Conclusions........10
Appendix 1. Populations stratified according to the mother intellectual........15
Appendix 2. Simple and multiple linear regression result of children phthalate concentration and maternal intelligence ........16
Appendix 3. Simple and multiple logistic regression result of children Phthalate concentration and maternal intelligence levels........17
Appendix 4. The chemical structures of common used phthalates, and their metabolites........18
Reference........20

Part II.

Contents
摘要........x
Abstract........xii
Contents........xiv
Contents of figures........xv
Contents of tables........xvi
Introduction........23
Materials and Methods........25
Study design and participants........25
Exposure assessment........25
The Swanson, Nolan, and Pelham IV scale (SNAP-IV)........27
Child Behavior Checklist (CBCL)........27
Strengths and Difficulties Questionnaire (SDQ)........28
Covariates........29
Statistical Analysis........30
Discussion........33
Appendix 1. The scoring of SNAP-IV items........43
Appendix 2. The scoring of items for CBCL........44
Appendix 3. The Classification for 25 SDQ items and each 5 domains........45
Appendix 4. Compare PFCs level in this study with similar target study........46
Appendix 5. Compare with similar target study concerning PFCs and ADHD........47
Reference........48

Part I.

Reference
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Part II.
Reference
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14. 探討血清全氟碳化合物與肝功能、甲狀腺功能、血糖調控與心血管疾病危險因子之相關
15. 產前全氟碳化物暴露可能改變八歲孩童時期肺功能